This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We are evaluating the protective potential of the small molecule CCR5 inhibitor, maraviroc as a vaginal microbicide. Maraviroc (Pfizer Inc) is now an FDA-licensed drug for the treatment of HIV-1 infection, and it has been licensed to the International Partnership for Microbicides (IPM) for development as a microbicide. However, its efficacy for this purpose has not been established, a gap we are currently exploring in partnership with John Moore, Cornell University. A preliminary experiment earlier this year that indicated that maraviroc is likely to be protective. In the preliminary experiment, we showed that a simple HMC-gel formulation of pharmaceutical grade maraviroc protected 5 of 5 macaques from vaginal challenge with the R5 SHIV-162P3 challenge virus. In contrast, both macaques challenged with the X4 SHIV-KU1 virus in the presence of the same maraviroc concentration were infected, as expected given maraviroc's mechanism of action. All the macaques received a single vaginal application of 4 ml of maraviroc at 0.75 mg/ml (3 mg total), 30 min prior to vaginal challenge. These studies are encouraging, but require confirmation and expansion to become definitive enough for publication, thus we are continuing these studies throughout the next several months.